Association of class I, II, and III MHC gene products with systemic lupus erythematosus. Results of a Central European multicenter study.

Class I, II, and III MHC gene products were examined in 248 Central European SLE patients. The previously reported association with HLA-A1, -B8 and -DR3, and C4AQ0 alleles was confirmed. The frequency of HLA-DR2 was also slightly elevated in SLE patients, while no increase in C4BQ0 alleles was observed. Additional findings were a significantly increased frequency of HLA-B13 and a significant decrease of HLA-B44.

Autoreactive T cells in rheumatic disease. II. Function and specificity of an autoreactive T helper cell clone established from a HLA-B27+ reactive arthritis.

T cell lines were established by limiting dilution of peripheral blood (PBL) and synovial fluid lymphocytes (SFL) of a patient with HLA-B27+ reactive arthritis. Among these cell lines, the CD4 phenotype was dominant. Functionally, the majority of these cell lines exhibited helper activity for the immunoglobulin production by autologous B cells and proliferated in response to autologous mononuclear cells. In most cases, this autoreactive response was associated with alloreactivity. Only one cell line, the autoreactive CD4+ T cell clone, UA-S2, which was derived from the synovial fluid, proliferated in a highly specific manner in response to a determinant associated with MHC class II products present on autologous mononuclear cells. The restriction element was shown to be associated with DR molecules by inhibition experiments with monoclonal antibodies. Within the patient's family, the capacity of mononuclear cells to stimulate a proliferative response of UA-S2 segregated together with the HLA haplotype A2 or 32, B27, Cw1, DRw11 which was contributed by the patient's mother. UA-S2 proved to be a functional helper T cell clone. In the absence of additional antigen or mitogen, it induced IgG and IgM synthesis of autologous and family members' B cells. This helper activity of UA-S2 showed the same MHC restriction as the proliferative response. Although the patient's father also typed DRw11, this haplotype was not recognized by UA-S2. It is suggested that this autoreactive T cell clone detects a microheterogeneity of the serologically defined DRw11 haplotype. Indeed, typing of the patient's family members with cellular reagents established a difference between the two DRw11 haplotypes.

Coagulation factor XIII A and B subunits in bone marrow and liver transplantation.

The polymorphism of the coagulation factor XIIIA and B subunits was determined before and after bone marrow or liver transplantation. It could be shown that the FXIIIA phenotype of the recipient was replaced by donor phenotype after bone marrow transplantation, whereas the phenotype of FXIIIB remained of recipient origin. In contrast, the FXIIIB phenotype changed to donor type after orthotopic liver transplantation but not the FXIIIA phenotype. The results indicate that the FXIIIA protein is produced in hemopoiesis, most likely in megakaryocytes and FXIIIB protein in the liver. Depending on the site of synthesis, FXIII alleles can be used as a marker in engraftment of FXIIIA-incompatible bone marrow transplantation or as a marker in FXIIIB-incompatible orthotopic liver transplantation.

[Does seronegative chronic polyarthritis have a special place? Clinical, biochemical and immunogenetic profile of early seronegative seropositive chronic polyarthritis]. / Sonderstellung der seronegativen chronischen Polyarthritis? Klinisches, biochemisches und immungenetisches Profil der frühen seronegativen und seropositiven chronischen Polyarthritis.

In the framework of an early-diagnosis out-patients clinic 100 patients (mean age 51 years), 82 of them female, were identified as highly suspicious of having chronic rheumatoid arthritis of recent onset (2-12 months). Five or more ARA criteria were present in 77 patients. IgM rheumatic factor was present in serum of 51 patients (latex-fixation test). A Waaler-Rose test of greater than or equal to 32 IU/ml was present in 21. After adjusting for alpha errors, there was a significantly higher prevalence of HLA-DR4 among those seropositive in the latex fixation test (64 vs 29%). A further 19 constitutional, anamnestic, clinical, biochemical and psychosocial criteria failed to reveal any different distribution between seropositive and seronegative cases. Using the specific definition of seropositivity in the Waaler-Rose test eliminated HLA-DR4 differences. The latter did not serve as a distinguishing criterion. There was only a marginal difference between DR4-positive and negative patients. These results fail to lend support to recent views of a special position of seronegative chronic rheumatoid arthritis.

[HLA and thyroid cancer]. / HLA und Schilddrüsencarcinom.

HLA typing was performed in 51 patients to analyse the pathogenetic background of differentiated and medullary thyroid carcinomas. A higher incidence of Bw62 and DR5 was observed in patients with papillary carcinoma (n = 24), DRw6 antigen in follicular carcinoma (n = 13), and DR3 antigen in patients with medullary carcinoma (n = 11). The DR3 antigen was present in one of two patients with a familial history of medullary thyroid carcinoma. Therefore, HLA typing is not suitable as a screening method for the detection of early thyroid carcinoma.

[Familial Mediterranean fever. Immunogenetic and rheumatologic aspects of the disease in a Turkish sibship]. / Familiäres Mittelmeerfieber. Immungenetische und rheumatologische Aspekte der Erkrankung in einer türkischen Sippschaft.

A family study was performed in 24 members of a Turkish sibship with familial Mediterranean fever (FMF) with 5 patients affected in 3 generations. The well-known autosomal-recessive inheritance of the disease was masked by a pseudodominant appearance, reflecting the striking frequency of congenial marriages. The immunogenetic investigation excluded a linkage between the expression of the disease and the HLA system. The arthritis of FMF was characterized typically by monarticular attacks in large joints of the lower limb. Frequently this manifestation led to diagnostic problems, particularly at the onset of the disease. No patient presented the clinical or radiological signs of sacroileitis. An observation of the disease process up to 3 years showed a benign prognosis of FMF-arthritis in 3 of 4 patients. Neither long-lasting functional impairment nor radiological signs of erosion had to be recognized. One patient suffered from a necrosis of the femoral head, possibly caused by the recurrent inflammation of the hip joint. Laboratory findings reflected the clinical picture of relapsing acute inflammation in an uncharacteristic manner. Their diagnostic significance exists mainly for the exclusion of other diseases.

Fourth component of complement (C4) polymorphism in human orthotopic liver transplantation.

C4 polymorphism was investigated in 13 orthotopic liver transplantations. It could be shown that recipient C4 phenotype disappears after transplantation and is replaced by donor phenotype on days 10-19 posttransplantation. This indicates that C4 is mainly produced in the liver. The delayed appearance of donor C4 phenotype compared with other complement components produced in the liver cannot be explained by different rates of synthesis or serum protein levels. The limited number of patients investigated in this study does not permit assessment of the role of C4, C3, Bf, and HLA-A, B, and DR in orthotopic liver transplantation.